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Biomedical subjects

B Safai

Publications and source records attributed to B Safai.

At least 55 records · Page 3Linked to original sources

HTLV-III in cells cultured from semen of two patients with AIDS.

Epidemiological results suggest that the etiological agent of the acquired immune deficiency syndrome (AIDS) is transmitted primarily through blood products, semen, and saliva. There is evidence that the human T-cell leukemia (lymphotropic) virus type III (HTLV-III) is this agent. HTLV-III has been isolated repeatedly from T cells obtained from peripheral blood or lymph node tissue of AIDS and pre-AIDS patients and of healthy people believed to have been exposed to the virus. In the present study, HTLV-III was detected in and isolated from T cells present in the seminal fluid of AIDS patients. Mononuclear cells from the semen of AIDS patients and normal individuals were cultured in the presence of T-cell growth factor (interleukin-2). After 6 to 8 days, HTLV-III antigens were transiently expressed by the cells from the AIDS patients but not by those from the normal individuals. When the mononuclear cells from the semen of AIDS patients were cocultured with a permissive human T-cell line, cell cultures were produced that expressed high levels of reverse transcriptase activity, showed retroviral particles by electron microscopy, and were positive for HTLV-III-specific antigens when tested by fixed-cell indirect immunofluorescence with the use of monoclonal antibodies to the p24 and p15 antigens of HTLV-III.

Acquired Immunodeficiency Syndrome↗

HTLV-I-specific antibody in AIDS patients and others at risk.

Serum samples from 440 acquired immunodeficiency syndrome (AIDS) patients or individuals at risk for AIDS were examined by the enzyme-linked immunosorbent assay technique for antibodies to HTLV-I core proteins. Specific antibodies were detected in 7% of AIDS patients, 7% of patients with lymphadenopathy, 0% of healthy homosexual men, and 12% of healthy Haitians. When findings in homosexual men were analysed separately, the prevalence for homosexual men with lymphadenopathy was 7% and for homosexuals with AIDS, 6%. Antibody titres ranged from 77 to 74 000. The antibody-positive cases included intravenous drug users, a Haitian AIDS patient, a recipient of multiple blood transfusions, and homosexual men. Haemophiliacs were not examined. Although HTLV-I-specific antibodies are more prevalent in AIDS patients than in healthy US donors, the difference is not sufficient to suggest an association of HTLV-I with the disease. The low rate may indicate an opportunisitic infection of AIDS patients by HTLV-I, or a crossreaction with the recently described HTLV variant, HTLV-III, believed to be the aetiological agent of AIDS. Whether HTLV-I normally exerts immune suppressive effects in vivo with biological consequences remains to be determined.

Acquired Immunodeficiency Syndrome↗

Seroepidemiological studies of human T-lymphotropic retrovirus type III in acquired immunodeficiency syndrome.

In a double-blind study, sera of 34 patients with acquired immunodeficiency syndrome (AIDS), 19 patients with lymphadenopathy syndrome, and 14 homosexual men with an increased risk of AIDS were screened for antibodies to proteins of the novel human T-lymphotropic retrovirus (leukaemia virus), HTLV-III, recently isolated from cultured T cells of AIDS patients. On a combination of a convenient and rapid enzyme-linked immunosorbent assay and a more sensitive electroblot (Western) assay, 100% of the AIDS sera were scored positive. Similarly, 84% of the lymphadenopathy patients were found to have serum antibodies to HTLV-III. A lower, but significant, proportion (21%) of healthy homosexual men with an increased risk of AIDS were also positive. No heterosexual controls, including those with heterophile antibodies during the course of infectious mononucleosis and patients with T-cell or B-cell lymphoma, had antibodies to HTLV-III. The results strongly indicate that the antibodies to HTLV-III are diagnostic of AIDS or indicate significant risk of the disease, and suggest that HTLV-III is the primary cause of human AIDS.

Acquired Immunodeficiency Syndrome↗

Frequent detection and isolation of cytopathic retroviruses (HTLV-III) from patients with AIDS and at risk for AIDS.

Peripheral blood lymphocytes from patients with the acquired immunodeficiency syndrome (AIDS) or with signs or symptoms that frequently precede AIDS (pre-AIDS) were grown in vitro with added T-cell growth factor and assayed for the expression and release of human T-lymphotropic retroviruses (HTLV). Retroviruses belonging to the HTLV family and collectively designated HTLV-III were isolated from a total of 48 subjects including 18 of 21 patients wih pre-AIDS, three of four clinically normal mothers of juveniles with AIDS, 26 of 72 adult and juvenile patients with AIDS, and from one of 22 normal male homosexual subjects. No HTLV-III was detected in or isolated from 115 normal heterosexual subjects. The number of HTLV-III isolates reported here underestimates the true prevalence of the virus since many specimens were received in unsatisfactory condition. Other data show that serum samples from a high proportion of AIDS patients contain antibodies to HTLV-III. That these new isolates are members of the HTLV family but differ from the previous isolates known as HTLV-I and HTLV-II is indicated by their morphological, biological, and immunological characteristics. These results and those reported elsewhere in this issue suggest that HTLV-III may be the primary cause of AIDS.

Acquired Immunodeficiency Syndrome↗

Granulocytic sarcoma. A new finding in the setting of preleukemia.

Preleukemia is a well-defined syndrome of hematopoietic dysfunction that may antedate the development of acute myelogenous leukemia. Granulocytic sarcoma refers to neoplastic infiltration in the skin, composed of immature cells of the granulocyte series. We report two cases of granulocytic sarcoma in the setting of preleukemia. The clinical importance of these cases, as well as the cutaneous manifestations of leukemia and the clinical spectrum of granulocytic sarcoma, are presented.

Aged↗

Kaposi's sarcoma. Gastrointestinal involvement correlation with skin findings and immunologic function.

We have evaluated 19 homosexual/bisexual male patients with biopsy-proven Kaposi's sarcoma (KS) of the skin in order to define the extent of gastrointestinal involvement and determine its correlation with oral mucosal disease, skin findings, and immunologic function. Nearly half the patients had oral mucosal lesions. In patients with oral mucosal lesions, 75% had gastrointestinal lesions. Some gastrointestinal involvement during the period of observation was present in 10 of the 19 patients. Involvement of the upper gastrointestinal tract was more common than colonic involvement: esophagus 1, stomach 8, duodenum 3, and colon 6. Significant immunosuppression was observed in these patients, measured in vitro by natural killer (NK) assay, and lymphocyte proliferation response to mitogens.

Adult↗

HLA-A,B,C and DR antigen frequencies in acquired immunodeficiency syndrome (AIDS) patients with opportunistic infections.

During the past three years, an epidemic of acquired immunodeficiency syndromes (AIDS) involving the presence of specific forms of cancer (notably Kaposi's sarcoma) and infection (e.g., pneumocystis carinii) ordinarily seen only in severely immunosuppressed hosts has occurred among active homosexuals, Haitian immigrants, drug users, and hemophiliacs in large cities in the United States and elsewhere. An as yet unidentified viral agent is presumably the cause of the initial immunodeficiency and host genetic factors may influence the subsequent development of different clinical symptoms in different patients. We have previously reported that the HLA antigens DR5 and DR2 are associated with susceptibility to Kaposi's sarcoma (KS) in different Caucasian subpopulations. We now have also noted that AIDS patients with opportunistic infections have a normal frequency of DR2 and DR5 and a significantly increased frequency of DR3 and that the ultimate clinical expression of AIDS in patients with unexplained lymphadenopathy may depend upon genetic factors associated with these particular DR types.

Acquired Immunodeficiency Syndrome↗

Ultraviolet-evoked prostaglandin biosynthesis in varying stages of keratinocyte differentiation in guinea pig skin.

Prostaglandin (PG) production by guinea pig epidermal cells was evaluated at various incubation intervals in normal and UV-exposed cultures. Prostaglandins have been implicated as mediators of the early phase of erythema in skin exposed to sunlight or UV-radiation. Using a density gradient centrifugation procedure, the epidermal cells were fractionated according to the various maturation stages of epidermal keratinocytes: high-density epidermal cells (HDEC) consisting of round, less mature cells; low-density epidermal cells (LDEC) consisting of polygonal keratinized cells; and intermediate-density epidermal cells (IDEC) consisting of both HDEC and LDEC. When cultures of 1 X 10(6) cells were incubated at 37 degrees C in 5% CO2 the highest concentrations of five PG moieties measured were present in supernatants from the LDEC cultures as compared to those of IDEC or HDEC. Levels of PGF 2 alpha were much higher than the rest, which were found in the order PGF2 alpha greater than PGE2 greater than PGE1 greater than 6-keto-PGF1 alpha greater than thromboxane (TX)B2. UV-irradiation induced increases in all but TXA2 production. These results identify and quantitate five compounds produced as a result of exaggerated activity of the cyclooxygenase induced by UV-irradiation.

Animals↗

Neurological complications of Kaposi's sarcomat. An analysis of 5 cases and a review of the literature.

We analyzed the neurological complications in 25 patients with Kaposi's sarcoma, 5 encountered at Memorial Sloan-Kettering Cancer Center and 20 culled from the literature. Patients with all clinical forms of Kaposi's sarcoma [14 classical cases, 2 African cases, 5 cases associated with immunosuppressive therapy and 4 cases associated with acquired immunodeficiency syndrome (AIDS)] suffered neurological dysfunction which included neoplastic involvement of the nervous system (Kaposi's sarcoma or another primary), autoimmune disorders and opportunistic infections. Neoplastic involvement was recorded most frequently in patients with classical and African Kaposi's sarcoma and was favored in a setting of extensive tumor dissemination. Opportunistic infections (cryptococcal meningitis and cerebral toxoplasmosis) were observed in all forms of Kaposi's sarcoma but were most frequent in AIDS cases and correlated with the degree of immune dysfunction. Our data suggest that more diverse opportunistic central nervous system infections, neurological disorders of an autoimmune nature, and neoplastic involvement of the nervous system are to be anticipated in AIDS.

Adult↗

Defective T-cell response to PHA and mitogenic monoclonal antibodies in male homosexuals with acquired immunodeficiency syndrome and its in vitro correction by interleukin 2.

We studied the ability of phytohemagglutinin (PHA) and two anti-T-cell monoclonal antibodies OKT3 and Pan T2, to induce proliferation and interleukin 2 (IL2) production in peripheral blood lymphocytes (PBL) from 21 homosexual patients: 12 with Kaposi's sarcoma (KS), 4 with reactive lymphadenopathy, and 5 with opportunistic infections. All patients with KS and opportunistic infections had significantly lower mitogen-stimulated DNA synthesis, as compared to the controls, irrespective of the mitogen used (P less than 0.01). The patients with lymphadenopathy exhibited significantly lower responses only in the OKT3 assay as compared to normals (P = 0.009). The production of endogenous IL2 was significantly lower in PBL cultures from patients with KS and with opportunistic infections, irrespective of the mitogen used, as compared to healthy male controls, and also significantly lower in the Pan T2-stimulated cultures from patients with lymphadenopathy. The addition of highly purified IL2 was able to restore partially lymphocyte proliferation in vitro in the presence of these mitogens in all patients. Our studies demonstrate (1) that male homosexuals even without clinical manifestations of immunodeficiency frequently exhibit a proliferative T-cell defect when anti-T-cell monoclonal antibodies rather than PHA are used as mitogens, (2) that this proliferative defect is associated with defective IL2 production, and (3) that this defect is at least in part correctable in vitro by highly purified IL2.

Acquired Immunodeficiency Syndrome↗

Analysis of T cell subsets in cancer patients treated with interferon.

T cell subsets were analyzed in 33 patients with advanced cancer who were treated with either of two interferon preparations: a partially purified human leukocyte interferon (HulFN-alpha (Le] and a highly purified recombinant interferon (lFLrA). Included in the lFLrA-treated group were eight patients with immunodeficiency and Kaposi's sarcoma. The OKT4+/OKT8+ ratio was used to define the balance between helper/inducer and suppressor/cytotoxic T cell subsets. With both interferon preparations, the mean OKT4+/OKT8+ ratio decreased 24 hours after the first interferon dose. Within the HulFN-alpha (Le) group, the decrease in ratio was related to an increase in OKT8+ cells; in the lFLrA group, it was accompanied by a small decrease in the proportion of OKT4+ cells that was greater than the decrease in OKT8+ cells. Patients treated with lFLrA were followed for the first three weeks of therapy. Most patients treated with lFLrA at all dose levels, ranging from 1 X 10(6) to 54 X 10(6) units per day, had a decrease in OKT4+/OKT8+ ratio on Day 1. No substantial change in the ratio was observed on Days 7, 14, and 22. Patients with immunodeficiency and Kaposi's sarcoma had responses similar to those of patients with other cancers treated with lFLrA. In conclusion, although both HulFN-alpha (Le) and lFLrA induce immediate decreases in the OKT4+/OKT8+ ratio, the T cell subset(s) primarily responsible for the decrease varies with the source of interferon.

Acquired Immunodeficiency Syndrome↗

Mucormycosis following bone marrow transplantation.

Disseminated mucormycosis, presenting with a cutaneous lesion, developed in a 20-year-old woman following bone marrow transplantation. The infecting organism was identified as Rhizopus rhizopodiformis. Despite early diagnosis and therapy with amphotericin B, the patient died.

Adult↗

Association of HLA-DR5 with mycosis fungoides.

Mycosis fungoides (MF) and Sézary syndrome (SS) are uncommon neoplasms of the lymphoreticular system with distinct clinical, histologic, and immunologic features. Based on the thymus-derived nature of the neoplastic cells, MF and SS are both classified as cutaneous T-cell lymphoma. While substantially greater understanding of MF and SS has been made possible, the exact mechanism for the initiation of either disease is still unknown. The possible involvement of environmental factors as well as viral etiology, i.e., retroviruses, has been suggested. In order to investigate the possible role of HLA-associated variations in genetic susceptibility, 74 patients with histologically documented MF were typed for HLA-A, -B, and -C antigens. Half of these patients were also typed for HLA-DR antigens. An increase in DR5 was the only statistically significant deviation in HLA antigen frequencies in these patients (53% in MF as compared with 20% in controls). An increased frequency of HLA-DR5 has also been associated with scleroderma and juvenile rheumatoid arthritis both of which have immunologic alterations. Also HLA-DR5 has been associated with renal cell carcinoma and Kaposi's sarcoma. The association of MF with DR5 suggests that some individuals with the DR5 antigen may be at higher risk for virally initiated and/or neoplastic diseases possibly through an HLA-linked defect in the immune system.

Adenocarcinoma↗